Efficacy and safety of ongericimab in patients with dyslipidemia: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

BACKGROUND

Ongericimab, a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, has recently been approved in China for hypercholesterolemia management but remains unapproved by major global regulatory agencies. This systematic review and meta-analysis provides the first pooled evidence on its efficacy and safety in participants with high cholesterol level.

OBJECTIVE

To evaluate the efficacy of ongericimab to reduce lipid levels compared with placebo, assess its effects on other atherogenic and antiatherogenic lipid parameters, and determine its safety profile in randomized controlled trials (RCTs).

METHODS

A comprehensive search of databases such as PubMed, Embase, and Cochrane Library from start to July 2025 identified RCTs comparing ongericimab with placebo. Primary outcome was percentage change in low-density lipoprotein cholesterol (LDL-C). Secondary outcomes included changes in other lipid parameters and safety endpoints. Data were pooled using a random-effects model, with heterogeneity assessed via the I² statistic.

RESULTS

Four double-blind, placebo-controlled RCTs (n = 736) conducted in China were included. Ongericimab produced a profound reduction in LDL-C (mean difference: -68.74%; 95% CI, -72.22% to -65.26; I² = 0%) and significantly lowered total cholesterol, apolipoprotein (Apo) B, non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and lipoprotein(a), with the latter showing a robust -54.66% reduction after sensitivity analysis. HDL-C (+10.87%) and ApoA1 (+8.12%) were modestly increased. Safety analyses showed no significant differences in rates of upper respiratory tract infections, urinary tract infections, hyperuricemia, hepatic enzyme elevations, cardiovascular events, or severe adverse events compared with placebo. Only injection site erythema was significantly higher (odds ratios: 5.57; P = .02), though events were mild and transient.

CONCLUSION

Ongericimab is a potent lipid-lowering agent with a favorable short-term safety profile, offering potential for patients requiring intensive LDL-C reduction. While findings are consistent and clinically compelling, they are derived solely from short-duration trials in Chinese populations and are limited to surrogate endpoints. Large, multiethnic cardiovascular outcomes trials are essential to confirm long-term benefits, assess rare adverse events, and establish its position among global lipid-lowering strategies.